Director / Ragon Institute of MGH, MIT and Harvard
Ragon Institute of MGH, MIT and Harvard 400 Technology Square Cambridge, MA 02139
Dr. Walker is a world leader in the study of immune control and evasion in HIV infection – he was the first to describe HIV-specific CD8+ T cells (with Robert Schooley and Martin Hirsch) and HIV-specific CD4+ T-cell responses, and he has defined the role and fate of these cells in acute and chronic HIV infection and transmission.
Dr. Walker’s laboratory focuses on mechanisms of immune control in HIV infection, focusing in particular on persons who control HIV infection spontaneously without the need for medication. Through an international collaboration now funded by the Gates Foundation, more than 1500 persons who control HIV infection to less than 2000 RNA Copies/mil without the need for antiviral medications have been recruited, and immunologic, virology and host genetic mechanisms accounting for this remarkable phenotype are being investigated.
Their results, published in Science, indicate that the major genetic determinants of HIV control affect the nature of the peptide-HLA binding. The lab is currently focusing its research efforts on this interaction and how it impacts the inductive and effector phases of the CD8 T cell response. Lab’s other projects that are currently underway are building on an observation that the antiviral efficacy of CTL varies dramatically among different epitopes and different restricting HLA alleles, in an attempt to define the major antiviral effector functions and apply these to vaccine development.
At the same time, they are working to define the subset of CD8 T cell responses that exert the strongest antiviral effect, and to define those responses that are simply passengers and fail to contribute to immune control. In addition to these efforts in Boston, Dr. Walker’s team is undertaking a major project at their laboratory at the Nelson Mandela School of Medicine at the University of KwaZulu-Natal, South Africa, where a major population based effort is underway to define the evolution of clade C virus infection under immune selection pressure, and to define the predictable pathways to immune escape.
The lab has established a mechanism for recruitment of persons with acute HIV infection by screening persons who test antibody negative at VCT (now HCT) sites in KZN. They anticipate an expanding collaboration with persons at the Ithembalabantu Clinic in Umlazi to accelerate these studies, which will include examination of tissue biopsies.